Primary extramedullary plasmacytoma: similarities with and differences from multiple myeloma revealed by interphase cytogenetics.

Primary extramedullary plasmacytoma is an indolent neoplasm that infrequently converts to multiple myeloma. Since cytogenetic data on extramedullary plasmacytoma are lacking, we studied 38 cases of this type of neoplasm by fluorescence in situ hybridization. Fourteen cases (37%) contained IGH breaks, including six with a t(4;14) translocation.

Expression of the local angiotensin II system in gastric cancer may facilitate lymphatic invasion and nodal spread.

Purpose: In this study we investigated the putative pathophysiological mechanism, by which angiotensin converting enzyme (ACE), and angiotensin II receptor (ATR) type 1 and 2 might contribute to cancer progression and lymph node metastasis in gastric cancer.

Materials And Methods: Local expression of ACE, AT1R and AT2R was investigated immunohistochemically in non-lesional tissue, primary tumors and lymph node metastases from 45 gastric cancer patients. The distribution of the ACE genotypes was studied in gastric cancer cell lines.

Differentiation between pancreaticobiliary and upper gastrointestinal adenocarcinomas: is analysis of cytokeratin 17 expression helpful?

Metastatic adenocarcinoma of unknown primary site, eg, to lymph nodes, liver, or lung, may originate from many organs. Microscopic differentiation of adenocarcinomas from the pancreaticobiliary and upper gastrointestinal tracts may be difficult because of shared histologic and immunohistologic features. A high prevalence of cytokeratin (CK)17 expression in pancreaticobiliary adenocarcinoma was reported, and preliminary data indicate infrequent or missing expression in gastric adenocarcinoma.

Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans.

MENX is a recessive multiple endocrine neoplasia-like syndrome in the rat. The tumor spectrum in MENX overlaps those of human multiple endocrine neoplasia (MEN) types 1 and 2. We mapped the MenX locus to the distal part of rat chromosome 4, excluding the homologs of the genes responsible for the MEN syndromes (RET and MEN1) and syndromes with an endocrine tumor component (VHL and NF1).

Usefulness of crush smears intraoperative consultaion of neurological biopsis.

Objective: To evaluate accuracy of intraoperative crush smears diagnosis of neurosurgical biopsies.

Design: Cross-sectional study.

Place And Duration Of Study: The Armed Forces Institute of Pathology, Rawalpindi, from February 2002 to February 2003.

Real-time quantitative RT-PCR shows variable, assay-dependent sensitivity to formalin fixation: implications for direct comparison of transcript levels in paraffin-embedded tissues.

Real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) is a versatile tool for precise quantification of gene expression. Formalin-fixed and paraffin-embedded (FFPE) tissue is well suited for qRT-PCR, if RNA extraction is optimized and small amplicon sizes are used. However, little is known whether individual assays may show variable sensitivity to fixation.

Diffuse large B-cell lymphoma with overexpression of cyclin e substantiates poor standard treatment response and inferior outcome.

Purpose: Gold standard to predict survival and stratify patients for risk-adapted therapy in diffuse large B-cell lymphoma (DLBCL) is the international prognostic index, although it does not consider the molecular heterogeneity of DLBCL. Deregulation of cyclin E (CCNE) is a strong predictor of poor prognosis in some neoplastic diseases. In tumor cells, it induces chromosomal instability with an increased rate of aneuploidy/polyploidy.

Endothelial cell survivin is involved in the growth of ovarian endometriotic cysts.

Background: The aim of the present study was to evaluate microvessel density (MVD) in the cellular layers of ovarian endometriomata, with particular interest in the relationship with VEGF and survivin expressions by endothelial cells and with the diameter of the cysts.

Materials And Methods: MVD and VEGF and survivin endothelial cell expressions were evaluated in 26 ovarian endometriotic cysts and correlated with the cyst diameter.

Results: The mean MVD was higher in the inner specialized stroma of ectopic endometrium than in the outer fibrous capsule, but only in the fibrous capsule was MVD correlated with endothelial cell VEGF and survivin expressions as well as with the cyst diameter.

Tissue microarray technology: principles, pitfalls and perspectives--lessons learned from hematological malignancies.

Detection, validation and incorporation into clinical use of new diagnostic, prognostic and therapeutic molecular targets in modern medical science should be time- and cost-efficient. Here, we discuss the principles, advantages, disadvantages and possible pitfalls of tissue microarray (TMA) technology, a powerful tool for high throughput large-scale morphological in situ analysis of molecular targets. Based on recent observations from molecular profiling of hematological malignancies, we review potential TMA applications assessing molecular targets in large collectives of tissue specimens.

Bone marrow changes in chronic myelogenous leukaemia after long-term treatment with the tyrosine kinase inhibitor STI571: an immunohistochemical study on 75 patients.

Aims: To carry out an immunohistochemical study on bone marrow (BM) biopsy specimens in 75 patients with chronic myelogenous leukaemia (CML) on long-term STI571 therapy.

Methods And Results: Sequential BM specimens taken at intervals of 21 +/- 6 months were investigated by enzyme- and immunohistochemistry including proliferating cell nuclear antigen and apoptosis. Evaluation was performed either by semiquantitative scoring or by morphometry (CD61+ megakaryopoiesis).

Effect of chemokine receptors CXCR4 and CCR7 on the metastatic behavior of human colorectal cancer.

Purpose: The expression of chemokine receptors CXCR4 and CCR7 has been associated with tumor dissemination and poor prognosis in a limited number of tumor entities. However, no data are currently available on the impact of chemokine receptor expression on disease progression and prognosis in human colorectal cancer.

Experimental Design: The expression of CXCR4 and CCR7 was evaluated in 96 patients with histologically confirmed colorectal cancers and in four colorectal cancer cell lines by immunohistochemical staining.

Expression of heat shock protein 70 (HSP70) at the interface of polymer-implants in vivo.

Synthetic polymer meshes are widely applied in the modern surgical approach for repairing abdominal wall defects. The implanted material is often observed leading to post-operative complications such as deficient abdominal wall mobility and adhesion formation with the abdominal cavity and/or abdominal organs. However, the functioning of the implant is primarily affected by the wound healing process guided by inflammatory events occurring at the tissue-material interface.

Lymphoma-specific genetic aberrations in microvascular endothelial cells in B-cell lymphomas.

Background: The growth of most tumors depends on the formation of new blood vessels. In contrast to genetically unstable tumor cells, the endothelial cells of tumor vessels are considered to be normal diploid cells that do not acquire mutations.

Methods: Using a combined immunohistochemical and fluorescence in situ hybridization assay, we examined the endothelial cells in 27 B-cell lymphomas for cytogenetic alterations that are known to be present in the lymphoma cells.

Different risk factors in basaloid and common squamous head and neck cancer.

Objectives/hypothesis: The prevalence of human papillomavirus (HPV), herpes simplex virus (HSV), cigarette smoking and alcohol abuse was compared between two histological subgroups of head and neck cancer.

Study Design: Retrospective review.

Methods: Paraffin-embedded, histologically confirmed surgical specimens from the oropharynx, hypopharynx and larynx, comprising 67 conventional squamous cell carcinomas (SCC) and 10 basaloid squamous cell carcinomas (BSCC), were analyzed for the presence of HPV and HSV DNA using polymerase chain reaction (PCR) techniques.

Real-time quantitative PCR of microdissected paraffin-embedded breast carcinoma: an alternative method for HER-2/neu analysis.

We studied the feasibility of using real-time quantitative PCR to determine HER-2 DNA amplification and mRNA expression in microdissected formalin-fixed, paraffin-embedded breast tumors and compared this with standard immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) methods. Study cases (27 carcinomas and 3 ductal breast carcinoma in situ (DCIS) cases) showed varying Her-2 expression as determined by IHC (HercepTest). In carcinomas, there was a good correlation between HER-2 DNA amplification and strong HER-2 protein expression detected by FISH and IHC, respectively.

Adhesion and migration of HRT-18 colorectal carcinoma cells on extracellular matrix components typical for the desmoplastic stroma of colorectal adenocarcinomas.

Colorectal carcinomas belong to the group of desmoplastic carcinomas which are characterized by an extensive connective tissue stromal component containing a variety of extracellular matrix (ECM) molecules. The biological importance of desmoplasia is still under discussion. Formerly, it has been regarded as walling off, thus being an obstacle for tumor cell invasion.

Intranodal palisaded myofibroblastoma with overexpression of cyclin D1.

Intranodal palisaded myofibroblastoma (IPM) is a rare benign spindle-cell tumor of lymph nodes with myofibroblastic/smooth muscle differentiation. We present another case of IPM that confirms the myofibroblastic differentiation of the tumor cells and identifies the so-called amianthoid fibers as collagen deposits by immunohistochemical and ultrastructural techniques. Because IPM shares histomorphologic characteristics with an inflammatory myofibroblastic tumor that has been associated with a virus-induced alteration of cell cycle regulation, the diagnostic approach was extended in this case.

Dynamics of fibrosis in chronic idiopathic (primary) myelofibrosis during therapy: a follow-up study on 309 patients.

Controversial issues in chronic idiopathic myelofibrosis (IMP) are amongst others the evolution of the disease process and the influence of therapy on the dynamics of fibrosis. For this reason, a multicenter observational study was performed on 309 patients with IMF that had a long follow-up including 822 bone marrow biopsies at a median interval of 32 months. In addition to a control group (156 patients) with symptomatic treatment, monotherapy consisted of busulfan (30 patients), hydroxyurea (52 patients), interferon (26 patients) and various combinations (48 patients).

Establishing the protein MIA (melanoma inhibitory activity) as a marker for chondrocyte differentiation.

Melanoma inhibitory activity (MIA), also referred to as cartilage derived retinoic acid-sensitive protein (CD-RAP), is detected physiologically in cartilage tissue and pathologically in malignant melanomas. To measure MIA/CD-RAP quantitatively we developed a sensitive ELISA system. Recently, we described diagnostic applications of the MIA-ELISA in patients with cartilage diseases.

Analysis of signal transducer and activator of transcription 3 (Stat 3) pathway in multiple myeloma: Stat 3 activation and cyclin D1 dysregulation are mutually exclusive events.

The signal transducer and activator of transcription molecules (Stats) play key roles in cytokine-induced signal transduction. Recently, it was proposed that constitutively activated Stat 3 (Stat 3 phosphorylated) contributes to the pathogenesis of multiple myeloma (MM) by preventing apoptosis and inducing proliferation. The study aim was to investigate Stat 3 activation in a series of multiple myeloma (MM) cases and its effect on downstream targets such as the anti-apoptotic proteins Bcl-xL, Mcl-1, and Bcl-2, and the cell-cycle protein cyclin D1.

Discordant bone marrow involvement in diffuse large B-cell lymphoma: comparative molecular analysis reveals a heterogeneous group of disorders.

Discordant bone marrow (BM) involvement in patients with a diagnosis of large-cell non-Hodgkin's lymphoma (NHL) is characterized by marrow infiltrates predominantly composed of small lymphoid cell, cytologically compatible with low-grade NHL. Although this phenomenon is well described morphologically, molecular data concerning the relationship of the two lesions are lacking. The aim of the study was to investigate the clonal relationship of discordant lymphoma manifestations by using immunoglobulin heavy chain gene (IgH), as well as bcl-2 rearrangements, as molecular markers.

Down-regulation of monocyte apoptosis by phagocytosis of platelets: involvement of a caspase-9, caspase-3, and heat shock protein 70-dependent pathway.

Monocytes interact and cross-talk with platelets in many settings including inflammation, hemostasis, or vascular disorders. During inflammatory diseases, there is a rapid targeting of monocytes and platelets to points of inflammation and endothelial injury, where they lie side-by-side. In this in vitro study, we investigated different interactions between monocytes and platelets and elucidated whether platelets might affect monocyte apoptosis.

Essential thrombocythemia with ringed sideroblasts: a heterogeneous spectrum of diseases, but not a distinct entity.

Background And Objectives: According to the recently published WHO-classification essential thrombocythemia with ringed sideroblasts (ET/RS) remains an ambiguous category which may be considered as myelodysplastic/myeloproliferative disease, unclassifiable. Because until now only case reports or very small series of patients have been described, a more systematically performed study is warranted.

Design And Methods: A retrospective evaluation was carried out on 38 patients with the diagnosis of ET/RS and more than 15 % ringed sideroblasts on smears.

Prospective evaluation of circulating hepatocytes by alpha-fetoprotein messenger RNA in patients with hepatocellular carcinoma.

Background: The significance of alpha-fetoprotein (AFP) messenger RNA as a surrogate marker for isolated tumor cells in the blood of patients with hepatocellular carcinoma (HCC) is controversial. Our goals were to correlate AFP mRNA with tumor recurrence and overall survival after patients with HCC received curative operations and to analyze AFP mRNA findings in control patients.

Methods: In this prospective controlled study, RNA was purified from the blood of 85 patients with HCC before, during, and after therapy and from 116 control patients.